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101.
Differential activation of nitric-oxide synthase isozymes by calmodulin-troponin C chimeras 总被引:3,自引:0,他引:3
Newman E Spratt DE Mosher J Cheyne B Montgomery HJ Wilson DL Weinberg JB Smith SM Salerno JC Ghosh DK Guillemette JG 《The Journal of biological chemistry》2004,279(32):33547-33557
The interactions of neuronal nitric-oxide synthase (nNOS) with calmodulin (CaM) and mutant forms of CaM, including CaM-troponin C chimeras, have been previously reported, but there has been no comparable investigation of CaM interactions with the other constitutively expressed NOS (cNOS), endothelial NOS (eNOS), or the inducible isoform (iNOS). The present study was designed to evaluate the role of the four CaM EF hands in the activation of eNOS and iNOS. To assess the role of CaM regions on aspects of enzymatic function, three distinct activities associated with NOS were measured: NADPH oxidation, cytochrome c reduction, and nitric oxide (*NO) generation as assessed by the oxyhemoglobin capture assay. CaM activates the cNOS enzymes by a mechanism other than stimulating electron transfer into the oxygenase domain. Interactions with the reductase moiety are dominant in cNOS activation, and EF hand 1 is critical for activation of both nNOS and eNOS. Although the activation patterns for nNOS and eNOS are clearly related, effects of the chimeras on all the reactions are not equivalent. We propose that cytochrome c reduction is a measure of the release of the FMN domain from the reductase complex. In contrast, cytochrome c reduction by iNOS is readily activated by each of the chimeras examined here and may be constitutive. Each of the chimeras were co-expressed with the human iNOS enzyme in Escherichia coli and subsequently purified. Domains 2 and 3 of CaM contain important elements required for the Ca2+/CaM independence of *NO production by the iNOS enzyme. The disparity between cytochrome c reduction and *NO production at low calcium can be attributed to poor association of heme and FMN domains when the bound CaM constructs are depleted of Ca2+. In general cNOSs are much more difficult to activate than iNOS, which can be attributed to their extra sequence elements, which are adjacent to the CaM-binding site and associated with CaM control. 相似文献
102.
103.
Tran Thu Hoa Le Hong Duc Rachele Isticato Loredana Baccigalupi Ezio Ricca Pham Hung Van Simon M. Cutting 《Applied microbiology》2001,67(9):3819-3823
Bacterial spores are being consumed as probiotics, although little is known about their efficacy or mode of action. As a first step in characterizing spore probiotics, we have studied the persistence and dissemination of Bacillus subtilis spores given orally to mice. Our results have shown that spores do not appear to disseminate across the mucosal surfaces. However, we found that the number of spores excreted in the feces of mice was, in some experiments, larger than the original inoculum. This was an intriguing result and might be explained by germination of a proportion of the spore inoculum in the intestinal tract, followed by limited rounds of cell growth and then sporulation again. This result raises the interesting question of whether it is the spore or the germinated spore that contributes to the probiotic effect of bacterial spores. 相似文献
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106.
Lei P Ayton S Finkelstein DI Spoerri L Ciccotosto GD Wright DK Wong BX Adlard PA Cherny RA Lam LQ Roberts BR Volitakis I Egan GF McLean CA Cappai R Duce JA Bush AI 《Nature medicine》2012,18(2):291-295
The microtubule-associated protein tau has risk alleles for both Alzheimer's disease and Parkinson's disease and mutations that cause brain degenerative diseases termed tauopathies. Aggregated tau forms neurofibrillary tangles in these pathologies, but little is certain about the function of tau or its mode of involvement in pathogenesis. Neuronal iron accumulation has been observed pathologically in the cortex in Alzheimer's disease, the substantia nigra (SN) in Parkinson's disease and various brain regions in the tauopathies. Here we report that tau-knockout mice develop age-dependent brain atrophy, iron accumulation and SN neuronal loss, with concomitant cognitive deficits and parkinsonism. These changes are prevented by oral treatment with a moderate iron chelator, clioquinol. Amyloid precursor protein (APP) ferroxidase activity couples with surface ferroportin to export iron, but its activity is inhibited in Alzheimer's disease, thereby causing neuronal iron accumulation. In primary neuronal culture, we found loss of tau also causes iron retention, by decreasing surface trafficking of APP. Soluble tau levels fall in affected brain regions in Alzheimer's disease and tauopathies, and we found a similar decrease of soluble tau in the SN in both Parkinson's disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. These data suggest that the loss of soluble tau could contribute to toxic neuronal iron accumulation in Alzheimer's disease, Parkinson's disease and tauopathies, and that it can be rescued pharmacologically. 相似文献
107.
The egg parasitoid Telenomus busseolae Gahan (Hymenoptera: Scelionidae) is one of the most important natural enemies of the Mediterranean corn stem borer, Sesamia nonagrioides Lefebvre (Lepidoptera: Noctuidae). The effects of lethal and sublethal concentrations of two commonly used pyrethroids, deltamethrin
and cyfluthrin, on emergence, fecundity, longevity, and offspring sex ratio of T. busseolae exposed during different preimaginal stages were studied. The insecticide, the tested concentrations of the insecticide (field-recommended
concentration and three dilutions with twofold concentration decreases), and the stage of parasitoid preimaginal development
(first and second larval stages and pupae) all significantly influenced the percentage of emergence. Life history parameters
of parasitoids exposed to the highest and lowest tested concentrations of the two insecticides (3.0 and 0.375 ml l−1 for cyfluthrin and 0.5 and 0.0625 ml l−1 for deltamethrin) at eight days post-oviposition (pupal stage) were calculated. The intrinsic rate of increase, the total
progeny produced, and the net reproductive rate of the parasitoid were all adversely affected by the field-recommended concentrations
of at least one insecticide. However, the longevity, the length of the oviposition period, and the offspring sex ratio were
unaltered by the two insecticides. The effects of sublethal concentrations of the insecticides, applied at preimaginal stages,
on the responses of T.
busseolae females to host abdominal scales, were studied in open-arena bioassays. Cyfluthrin altered both the residence time and linear
speed of the parasitoid in the host scale-containing areas, whereas deltamethrin had no effect. Our results indicate that,
in addition to lethal effects, sublethal effects should also be considered when evaluating insecticide consequences on non-targets. 相似文献
108.
Summary Studies on ragweed have been carried out in the province of Trieste (Northern Italy) in which it is becoming widespread. The floristic records, the increasing amount of airborne pollen monitored and the relevant skin reactivity are reported. This phenomenon, though still at the beginning, is actually showing an upward trend due to man's intervention over wider and wider areas which as a consequence become suitable for the settlement of these anthropophitic species. The aerobiological data are compared to the skin reactivities of allergic subjects. 相似文献
109.
L Mauro M Salerno M L Panno D Bellizzi D Sisci A Miglietta E Surmacz S Andò 《Biochemical and biophysical research communications》2001,288(3):685-689
This study demonstrates how the potentiating effects of E2 on insulin signaling in ER-positive breast cancer cells are consequent to an enhanced IRS-1 expression [corrected]. It induces an increase of both PI-3K/AKT and ERK1/2 activities. A direct action of E2 in the regulating mouse IRS-1 gene is also investigated in both Chinese hamster ovary and MCF-7 cells that are transfected with mouse IRS-1 regulatory sequences. The authors have reported, for the first time, how E2 induction of IRS-1 mRNA was correlated with a direct positive regulatory role of E2 on the IRS-1 promoter. This effect seems to be not strictly related to the cell type. 相似文献
110.
Natuzzi D Daddabbo L Stipani V Cappello AR Miniero DV Capobianco L Stipani I 《Journal of bioenergetics and biomembranes》1999,31(6):535-541
The effect of pyridoxal 5-phosphate and some other lysine reagents on the purified,reconstituted mitochondrial oxoglutarate transport protein has been investigated. The inhibition ofoxoglutarate/oxoglutarate exchange by pyridoxal 5-phosphate can be reversed by passing theproteoliposomes through a Sephadex column but the reduction of the Schiff's base by sodiumborohydride yielded an irreversible inactivation of the oxoglutarate carrier protein. Pyridoxal5-phosphate, which caused a time- and concentration-dependent inactivation of oxoglutaratetransport with an IC50 of 0.5 mM, competed with the substrate for binding to the oxoglutaratecarrier (K
i
= 0.4 mM). Kinetic analysis of oxoglutarate transport inhibition by pyridoxal5-phosphate indicated that modification of a single amino acid residue/carrier molecule wassufficient for complete inhibition of oxoglutarate transport. After reduction with sodiumborohydride [3H]pyridoxal 5-phosphate bound covalently to the oxoglutarate carrier. Incubation ofthe proteoliposomes with oxoglutarate or L-malate protected the carrier against inactivationand no radioactivity was found associated with the carrier protein. In contrast, glutarate andsubstrates of other mitochondrial carrier proteins were unable to protect the carrier. Mersalyl,which is a known sulfhydryl reagent, also failed to protect the oxoglutarate carrier againstinhibition by pyridoxal 5-phosphate. These results indicate that pyridoxal 5-phosphateinteracts with the oxoglutarate carrier at a site(s) (i.e., a lysine residue(s) and/or the amino-terminalglycine residue) which is essential for substrate translocation and may be localized at or nearthe substrate-binding site. 相似文献